CN104587524B - Beta-TCP/PGS composite scaffold and preparation method and application thereof - Google Patents
Beta-TCP/PGS composite scaffold and preparation method and application thereof Download PDFInfo
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- CN104587524B CN104587524B CN201510012513.9A CN201510012513A CN104587524B CN 104587524 B CN104587524 B CN 104587524B CN 201510012513 A CN201510012513 A CN 201510012513A CN 104587524 B CN104587524 B CN 104587524B
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Abstract
The invention discloses a Beta-TCP/PGS composite scaffold and a preparation method and application thereof. The Beta-TCP/PGS composite scaffold comprises PGS (poly glycerol sebacate) and a Beta-TCP (Tertiary Calcium Phosphate) porous scaffold. Particularly, the Beta-TCP/PGS composite scaffold is prepared by impregnating the Beta-TCP porous scaffold with a PGS prepolymer solution and then preforming thermal-crosslinking and drying. The invention further discloses a medicine composition and a tissue-engineered bone repair material, which comprise the composite bracket. Compared with a pure Beta-TCP porous scaffold, the Beta-TCP/PGS composite scaffold prepared by the invention shows excellent tenacity and compression strength, meanwhile has favorable biocompatibility and can be used as a bone repair material and a medicine carrier material.
Description
Technical field
The present invention relates to a kind of bone tissue reparation bata-tricalcium phosphate/macromolecular material compound rest system and its preparation side
Method and application, and in particular to a kind of bata-tricalcium phosphate/poly- decanedioic acid glyceride compound rest system and preparation method and application.
Background technology
Bata-tricalcium phosphate (β-TCP) is similar with the main inorganic composition in mankind's natural bone, with good bio-compatible
Property and biological degradability and excellent synosteosis ability, and with higher hardness and rigidity, be easy to accelerate to repair bone tissue,
Thus obtain a wide range of applications in bone tissue reparation engineering, it is also one of most widely used bone renovating material so far.Its
In, especially it is easy for cell and the β-TCP porous support materials that grow into obtains the extensive concern of domestic and international researcher.But it is single
Bata-tricalcium phosphate porous support there are problems that fragility is big, bad mechanical strength, stability, this affects to a certain extent
Its clinical application effect, especially in terms of stress carries Bone Defect Repari.
In order to solve this problem, researcher has developed β-TCP/ macromolecule compound rests.Research shows, with other thermoplastics
Property degradable material (such as polylactide and its copolymer) is combined in a certain way, can to a certain extent improve the strong of bata-tricalcium phosphate
Degree and stability (Oral Max Surg 2008,37,929-934).However, because the toughness of these polymer itself is poor,
It is limited to the toughness and strength improving of β-TCP.The content of simultaneously too high macromolecular material can be produced to the biologically active of β-TCP
Affect.
Therefore, this area is still needed deep research and development β-TCP/ macromolecule compound rests.
The content of the invention
It is an object of the invention to provide a kind of new bata-tricalcium phosphate/poly- decanedioic acid glyceride compound rest and preparation
Methods and applications.
A first aspect of the present invention, there is provided a kind of bata-tricalcium phosphate/poly- decanedioic acid glyceride compound rest, the composite support
Frame is made up of poly- decanedioic acid glyceride and bata-tricalcium phosphate porous support.
In another preference, the compound rest is compounded on bata-tricalcium phosphate porous support by poly- decanedioic acid glyceride
Constitute.
In another preference, the compound rest includes：The poly- decanedioic acid glyceride of 10～25wt% and 75-90wt% β-
Tricalcium phosphate, with the gross weight meter of the compound rest.
In another preference, the bata-tricalcium phosphate porous support porosity is 70%-95%.
In another preference, the bata-tricalcium phosphate porous support average pore size is 300-500 microns.
In another preference, the compound rest has following one or more features：
(1) porosity is 70%-95%, preferably 85-95%, is more preferably 90-95%；
(2) average pore size is 300-500 microns；
(3) greatest compressive strength that can be born before supporting structure destruction is 0.015-2MPa；
(4) the largest deformation amount that can occur before supporting structure destruction is 120%-750%；
(6) bata-tricalcium phosphate and the mass ratio of the poly- decanedioic acid glyceride are 1：0.1-0.35, preferably 1：
0.18。
In another preference, the bata-tricalcium phosphate porous support is made up of nanoscale bata-tricalcium phosphate, the nanometer
The average grain diameter of level bata-tricalcium phosphate is 300-500 nanometers.
A second aspect of the present invention, there is provided the preparation method of the compound rest described in first aspect, the preparation method bag
Include following steps：
A bata-tricalcium phosphate porous support impregnated in acquisition β-tricresyl phosphate in poly- decanedioic acid glyceride prepolymer solution by ()
Calcium/poly- decanedioic acid glyceride compound rest；
B step a) acquisition bata-tricalcium phosphate/poly- decanedioic acid glyceride compound rest heat cross-linkings are obtained being crosslinked support by ()；
C the crosslinking support that step b) is obtained is dried to obtain the compound rest by ().
In another preference, the concentration of the poly- decanedioic acid glyceride prepolymer solution is 10-35mg/ml, the β-
Tricalcium phosphate is 1 with the mass ratio of the poly- decanedioic acid glyceride performed polymer：0.1-0.35, preferably 1：0.18.
In another preference, the poly- decanedioic acid glyceride prepolymer solution solvent for use is alcohols solvent, dimethyl
Sulfoxide, chloroform, dichloromethane, the alcohols solvent is preferably ethanol.
In another preference, the bata-tricalcium phosphate porous support is made up of nanoscale bata-tricalcium phosphate, the nanometer
The average grain diameter of level bata-tricalcium phosphate is 300-500 nanometers.
In another preference, bata-tricalcium phosphate porous support is prepared using polyurethane foam infusion process.Specifically, by β-
Tricalcium phosphate solution is mixed and made into slurry with solvent, makes slurry uniformly be poured into foam in the slurry polyurethane foam dipping,
Foam is sintered after solvent volatilizees completely from the foam for having irrigated (it is preferred that being sintered using gradient temperature, sintering temperature
Spend for 200-800 DEG C), remove polyurethane foam and obtain bata-tricalcium phosphate porous support.
In another preference, the preparation of the poly- decanedioic acid glyceride performed polymer is comprised the following steps：
It is 1 by mol ratio under the atmosphere of (i) argon gas:1 decanedioic acid and glycerine are in 120-140 DEG C of (preferable 130 DEG C) reactions
18-36 hours (preferable 24 hours)；
(ii) product of step i) is placed in into 18-36 hours (preferable 24 under 120-140 DEG C of (preferable 130 DEG C), vacuum condition
Hour), obtain thick PGS performed polymers；
(iii) dialysis purification step ii) obtain thick PGS performed polymers obtain purify described poly- decanedioic acid glyceride pre-polymerization
Body.
In another preference, the molecular weight of the poly- decanedioic acid glyceride performed polymer is 12000 dalton.
In another preference, the coefficient of dispersion of the poly- decanedioic acid glyceride performed polymer is 1.19.
In another preference, the drying is referred to：
(1) vacuum freeze drying；
(2) it is vacuum dried；(being dried including secondary vacuum)
(3) vacuum freeze drying after being vacuum dried；
(4) freeze after being vacuum dried.
In another preference, step b) be dried before also include solvent flashing the step of.
In another preference, the condition of (1) vacuum freeze drying is as follows：- 40 DEG C～-60 DEG C vacuum freeze dryings
20-30 hours.
In another preference, the condition of (1) vacuum freeze drying is as follows：- 50 DEG C of vacuum freeze dryings 24 hours.
In another preference, (2) vacuum drying condition is as follows：120-140 DEG C of vacuum drying 40-55 hour；
Or (2) vacuum drying condition is as follows：After 120-140 DEG C of vacuum drying 40-55 hour, 20-30 DEG C of vacuum drying 20-
30 hours.
In another preference, (2) vacuum drying condition is as follows：130 DEG C are vacuum dried 48 hours；Or it is described
(2) vacuum drying condition is as follows：After 130 DEG C are vacuum dried 48 hours, 25 DEG C are vacuum dried 24 hours.
In another preference, the condition of vacuum freeze drying is as follows after described (3) vacuum drying：120-140 DEG C of vacuum
After being dried 40-55 hours, -10 DEG C to -80 DEG C vacuum freeze drying 20-30 hours.
In another preference, the condition of vacuum freeze drying is as follows after described (3) vacuum drying：130 DEG C of vacuum drying
After 48 hours, -20 DEG C to -50 DEG C vacuum freeze dryings 24 hours.
In another preference, the condition freezed after described (4) vacuum drying is as follows：120-140 DEG C of vacuum drying 40-55
It is placed in -80 DEG C to -200 DEG C after hour to freeze -2 minutes 24 hours.
In another preference, the condition freezed after described (4) vacuum drying is as follows：After 130 DEG C are vacuum dried 48 hours
It is placed in -80 DEG C to -200 DEG C to freeze -2 minutes 24 hours.
A third aspect of the present invention, there is provided a kind of pharmaceutical composition, described pharmaceutical composition is included：
Compound rest described in first aspect；With
For promoting the medicine and/or growth factor of Bone Defect Repari and/or growth.
In another preference, the medicine selected from dexamethasone, gentamicin, methotrexate (MTX), aceclofenac, 1,
25- dihydroxyvitamin Ds, Lovastatin, simvastatin etc..
In another preference, the growth factor is selected from：Bone morphogenic protein BMP-2 is (such as BMP-2, BMP-4, BMP-
7), VEGF, Basic Fibroblast Growth Factor, TGF, hypoxia inducible transcription factor, BMP conversions
Growth factor family (TGFs), fibroblast growth factor (FGF), platelet derived growth factor (PDGF), Insulin-Like
Growth factor (IGF).
A kind of a fourth aspect of the present invention, there is provided tissue engineering bone renovation material, the tissue engineering bone renovation material bag
Contain：
Compound rest described in first aspect；With
For promoting the cell of Bone Defect Repari and/or growth.
In another preference, the cell is selected from：Mesenchymal stem cells MSCs and endothelial cell.
In another preference, the tissue engineering bone renovation material also includes promoting the medicine of Bone Defect Repari and/or growth
And/or growth factor.
A fifth aspect of the present invention, there is provided the purposes of the compound rest described in first aspect, is selected from the group：
(1) for preparing osseous tissue renovating material；
(2) as drug carrier material；
(3) as tissue engineering bracket material.
A sixth aspect of the present invention, there is provided the purposes of the pharmaceutical composition described in the third aspect, repaiies for preparing bone tissue
Answer material or as drug carrier material or as tissue engineering bracket material.
Poly- decanedioic acid glyceride is compounded in the present invention surface of bata-tricalcium phosphate support so that the β-tricresyl phosphate of the present invention
Calcium/poly- decanedioic acid glyceride compound rest system not only has excellent mechanical property and biocompatibility, and with promotion
Vascularization further promotes Bone Defect Repari.This new bone repairing support can be applicable to the treatment of internal bone injury so that damage
The injury of the bone can quickly be repaired.
It should be understood that within the scope of the present invention, above-mentioned each technical characteristic of the present invention and have in below (eg embodiment)
Can be combined with each other between each technical characteristic of body description, so as to constitute new or preferred technical scheme.As space is limited, exist
This no longer tires out one by one states.
Description of the drawings
Fig. 1 is purifying PGS performed polymers prepared by embodiment 11H-NMR and IR schemes.
Fig. 2 is the gpc chromatogram of purifying PGS performed polymers prepared by embodiment 1.
Fig. 3 is support shape appearance figure.
Fig. 4 is scanning electron microscope (SEM) photograph.
Fig. 5 is the TGA and XRD of compound rest prepared by embodiment 10.
Fig. 6 is to carry out manual compression to β-TCP porous supports (embodiment 2) and β-TCP/15P-CFV (embodiment 10)
Result figure.
Fig. 7 is the continuity testing result and porosity figure of β-TCP porous supports and compound rest.
Fig. 8 is mechanical experimental results.
Fig. 9 schemes over time for the pH value and weight of external degradation.
Figure 10 schemes for the SEM and EDS of the β-TCP supports and compound rest mineralising in SBF solution.
Figure 11 is MTT test result figures.
Figure 12 is Laser Scanning Confocal Microscope figure.
Specific embodiment
Present inventor develops first a kind of new bata-tricalcium phosphate/gather through extensively and in depth studying
Decanedioic acid glyceride compound rest, can be effectively improved the fragility of simple bata-tricalcium phosphate porous support, while with good life
Thing compatibility.Acid produced by the catabolite of PGS can be used to regulate and control the degradation speed of β-TCP, so that the degraded of compound rest
Speed matches with new bone formation speed, so as to improve the Bone Defect Repari ability and new bone growth ability of material, realizes that bone tissue is complete
Full regeneration/repair.On this basis, the present invention is completed.
Bata-tricalcium phosphate/poly- decanedioic acid glyceride compound rest
In the present invention, compound rest, complex stephanoporate bracket, compound rest system have identical implication.
The compound rest of the present invention, is made up of poly- decanedioic acid glyceride and bata-tricalcium phosphate porous support.
Poly- decanedioic acid glyceride (PGS) is a kind of elastomer of good biocompatibility, with good toughness and biological drop
Solution performance, with the effect for promoting vascularization.Meanwhile, the catabolite of PGS is in acidity, and early stage β-TCP material degradations product
In alkalescence, the two compound can reduce material, and because of degraded, caused pH excessively floats the internal aseptic inflammation generation for causing
Possibility.Meanwhile, the acid produced by the catabolite of PGS can be used to regulate and control the degradation speed of β-TCP, so that compound rest
Degradation speed matches with new bone formation speed, so as to improve the Bone Defect Repari ability and new bone growth ability of material, realizes bone group
Cast off and regenerate entirely/repair.
The average pore size of compound rest is 300-500 microns, and porosity is 70-95%.
Inventors be surprised to learn that, compared with other macromolecular materials such as PCL, PLA, poly- decanedioic acid glyceride and β-phosphorus
Sour DFP porous support is combined the compound rest for obtaining, and is remarkably improved mechanical property.
The greatest compressive strength that can be born before the destruction of compound rest structure is 0.015-2MPa, preferably 0.1-
2MPa, is more preferably 0.3-2MPa, or even 0.5-2MPa, most preferably 1.5-2 or 1-2MPa.
The largest deformation amount that can occur before the destruction of compound rest structure is 120%-750%, preferably 150%-
650%, it is more preferably 200-500% or 300-400%.
The features described above that the present invention is mentioned, or the feature that embodiment is mentioned can be in any combination.Disclosed in this case specification
All features can be used in combination with any combinations thing form, each feature disclosed in specification, can by it is any provide it is identical,
The alternative characteristics of impartial or similar purpose replace.Therefore except there is special instruction, disclosed feature is only impartial or similar spy
The general example levied.
The invention has benefit that：
(1) a kind of new bata-tricalcium phosphate/poly- decanedioic acid glyceride compound rest is provided, relative to single β-tricresyl phosphate
Calcium porous support, improves its toughness, and composite has higher hardness and rigidity.
(2) catabolite of PGS is in acidity, and early stage β-TCP material degradations product is in alkalescence, and the compound of the two is expected to drop
Because of degraded, caused pH's low material excessively floats the possibility that the internal aseptic inflammation that causes occurs.
(3) bata-tricalcium phosphate/poly- decanedioic acid glyceride compound rest for preparing has good cell compatibility and biology
Mineralization ability, is expected to be used as bone renovating bracket material.
With reference to specific embodiment, the present invention is expanded on further.It should be understood that these embodiments are merely to illustrate the present invention
Rather than restriction the scope of the present invention.The experimental technique of unreceipted actual conditions in the following example, generally according to conventional strip
Part such as Sambrook et al., molecular cloning：Laboratory manual (New York:Cold Spring Harbor Laboratory
Press, 1989) described in condition, or according to the condition proposed by manufacturer.Unless otherwise indicated, otherwise percentage and
Number is calculated by weight.
Unless otherwise defined, all specialties used in text and scientific words and meaning familiar to one skilled in the art institute
Justice is identical.Additionally, any similar to described content or impartial method and material all can be applicable in the inventive method.Text
Described in preferable implementation only present a demonstration with material and be used.
Evaluation method
(1) Mechanics Performance Testing
Support is made into the sample of 10mm × 10mm × 10mm, then with universal testing machine (AG-2000,
Shimadzu, Japan) performance test is compressed, compression speed is 1mm/min.
(2) other performance characterizations are characterized
Purified rear point using gel permeation chromatography (GPC, SPD-M20A, Shimadzu Kyoto, Japan) analysis PGS
The change of son amount and dispersiveness.
The grand of material is prepared using SEM mirror (SEM, JSM-6360LV-4800, JEOL, Japan) observation
See the pattern change of structure and deposition mineralising.
Using X-Ray diffraction analysis (RINT2000 polycrystalline diffractometers) and TGA (TG 209, Netzch, Germany) heat point
The combining case of analysis analysis compound support frame material, according to Barrett-Joyner-Helen (BJH) formula average pore size is calculated.
Using laser confocal microscope (CLSM, Leica Microsystems) observe material surface cell morphology and
Infiltration.
(3) Cell culture invitro
Mouse mesenchymal stem cells MSCs (rBMSCs) is incubated at containing 10% hyclone, 100U/mL penicillin, 100U/mL
In the α-MEM nutrient solutions of streptomysin, in 37 DEG C, 5%CO2Secondary Culture in incubator.To be placed in after macropore support high-temperature sterilization
In 24 porocyte culture plates, rBMSCs is inoculated into respectively material surface, adds culture medium；It is incubated to culture after terminating and uses MTT
Determination method detects cytoactive and cell propagation, and to every hole the tetramethyl azo azoles salt reagent of 100 μ L is added, and 37 DEG C are continued to be incubated
After 4h, supernatant is abandoned in suction, adds 1mL DMSO, gently shakes 20min, dissolves crystal, is existed using continuous spectrum ELIASA
The absorbance value of solution is determined at 490nm.
Endothelial cell (HUVEC) be incubated at containing 10% hyclone, 100U/mL penicillin, 100U/mL streptomysins DMEM
In nutrient solution, in 37 DEG C, 5%CO2Secondary Culture in incubator.24 hole cell culture will be placed in after macropore support high-temperature sterilization
In plate, HUVEC is inoculated into respectively material surface, adds culture medium；It is incubated to culture after terminating and uses MTT determination methods to detect cell
Activity and cell propagation, to every hole the tetramethyl azo azoles salt reagent of 100 μ L is added, and 37 DEG C are continued to be incubated after 4h, and supernatant is abandoned in suction
Liquid, adds 1mL DMSO, gently shakes 20min, dissolves crystal, determines molten at 490nm using continuous spectrum ELIASA
The absorbance value of liquid.
By laser co-focusing (confocal laser scanning microscopy) observation of cell on support
Permeate and sprawl：By 2 × 104The cell culture in individual/hole PBS three times after 24h on material, 2.5% glutaraldehyde is fixed
It is PBS 5 times, every with the phalloidine (FITC-Phalloidin) of marked by fluorescein isothiocyanate dyeing 40min after 15min
Secondary 5min, then with PBS 5 times, each 5min after DAPI dyeing 10min, three are carried out under laser co-focusing after mounting fluid-tight piece
Dimension observation.
Embodiment 1
The synthesis of PGS performed polymers and purifying
PGS performed polymers are synthesized by two-step process.
The first step：Under the atmosphere of argon gas, mol ratio is 1:1 decanedioic acid and glycerine react 24 hours at 130 DEG C；
Second step：The product of the first step continues reaction 24 hours under 130 DEG C, vacuum condition, obtains PGS performed polymers.
Then purified, first dissolved PGS performed polymers in ethanol, the emulsion for obtaining is stood into a period of time, inclined
Go upper liquid.The PGS performed polymers for obtaining are positioned in bag filter, are dialysed, obtain molecular weight for 12000Da, dispersiveness
Coefficient is 1.19 purifying PGS performed polymers.
Purifying PGS performed polymers1In H-NMR such as Fig. 1 shown in A.1.31st, the proton peak master occurred at 1.62 and 2.35ppm
Show the presence of decanedioic acid unit in the macromolecular chain for synthesizing, the proton peak at 3.55-4.54ppm is then illustrated in macromolecule
There is the presence of glycerol unit in chain.To the further analysis of nuclear magnetic spectrum, it can be deduced that in PGS performed polymers, glycerine/decanedioic acid
Molar ratio be 1:1.In addition, the proton peak at 2.89ppm is the unreacted hydroxyl on glycerol unit.This also indicates that conjunction
Into macromolecule repetitive in there is a hydroxyl, while illustrating that the PGS performed polymers that obtain of synthesis are good linear structures
Macromolecule.
In the FTIR such as Fig. 1 of purifying PGS performed polymers shown in B, by by the infrared figure of decanedioic acid, glycerine and PGS performed polymers
After spectrum normalization, it is compared, it can be seen that decanedioic acid is 1603 and 1416cm-1(carboxylate groups asymmetric and symmetrically stretch
Contracting peak) there is obvious absworption peak, after the reaction, the infrared results of PGS performed polymers show, the remitted its fury at peak is in 1603 Hes
1416cm-1Place, in 1740cm-1Place occurs in that new peak, is ester bond (C ═ O) newly-generated after reaction.By result above
Show, successfully synthesize PGS performed polymers.
The GPC spectrograms of purifying PGS performed polymers are as shown in Figure 2.As can be seen that performed polymer is after purified, its molecular weight is
12000Da, the coefficient of dispersion is 1.19, obtains applicable PGS performed polymers.
Embodiment 2
The synthesis of β-TCP nano-particles and the preparation of β-TCP porous supports
By 0.4mol Ca (NO3)2·4H2O and 0.4mol (NH4)2HPO3In being dissolved in 200ml ultra-pure waters respectively, quick stirring
30min, obtains Ca salt and P salting liquids.Ca solution is dropwise added drop-wise to into (1-2 drop/sec) in P solution, while the stirring that remains a constant speed
With the ammoniacal liquor (2M) that addition is prepared the pH stable of mixed solution is adjusted 7.0～7.5.After being added dropwise to complete, stop stirring, will be molten
Liquid stands 2 hours, makes solution natural sedimentation, the clear liquid on upper strata of inclining.Then resulting precipitation is loaded into centrifugal bottle, is carried out
Centrifugation (6000r/min, 10min), the ultrapure washing of next step, ultrasonic (10min) continues to be centrifuged, then repeatedly washing 2 times,
Then washed one time with absolute ethyl alcohol again, take out product after the completion of centrifugation, dried (80 DEG C, 24 hours).
After drying, product is ground with mortar, be put into dry pot high temperature sintering, high temperature furnace setting program：25 DEG C～220 DEG C,
(195min, 1 DEG C/min), 220 DEG C～220 DEG C (120min, 1 DEG C/min), 220 DEG C～600 DEG C (380min, 1 DEG C/min),
600～600 DEG C (120min, 1 DEG C/min), 600～800 (200min, 1 DEG C/min), 800～800 DEG C (120min, 1 DEG C/
Min), terminate.
The size of the β-TCP nano-particles of synthesis is 300～500nm.
β-TCP porous supports are prepared using polyurethane foam infusion process.First by the β-TCP nanoparticle powders for preparing
Be configured to suitable slurry (1g β-TCP powder/800 microlitre) with absolute ethyl alcohol, by the polyurethane sponge for shearing (PU, 10mm ×
10mm × 3-10mm, in pattern such as Fig. 3 shown in a) it is impregnated into slurry so that and slurry is uniformly poured in sponge, then will
The sponge (in pattern such as Fig. 3 shown in b) for having irrigated is placed in drying box (60 DEG C, more than 48 hours) drying, until anhydrous second
Alcohol volatilization is complete.Then sponge bracket is sintered with Muffle furnace, temperature setting program is：25 DEG C～220 DEG C, (195min,
1 DEG C/min), 220 DEG C～220 DEG C (120min, 1 DEG C/min), 220 DEG C～600 DEG C (380min, 1 DEG C/min), 600～600
DEG C (120min, 1 DEG C/min), terminates.
Obtain in the pattern such as Fig. 3 of β-TCP porous supports shown in c, SEM is schemed as shown in A in Fig. 4 and B.
β-TCP the porous supports that can be seen that preparation by the shape appearance figure and SEM figure (A in Fig. 4) of support have good
Hole is connective, and the size in hole is in 300-500 microns.From Fig. 4 B can be seen that sintering after rack surface on β-TCP still
It is exist with the particle of nanometer shape, but is simply simply packed together.Porosity is 93 ± 2%.Greatest compressive strength is
0.01 ± 0.002MPa, tear type variable is 102 ± 15%.
Embodiment 3
The preparation of β-TCP/10P-Unc porous supports
By obtained PGS performed polymers (PGS-1:1, prepared by embodiment 1) concentration that is made into absolute ethyl alcohol as solvent is
10mg/ml solution.β-TCP porous supports (weight 0.2g) is placed in 24 orifice plates, PGS solution 2ml are added, makes support complete
Submergence, then orifice plate is placed in 3～5 hours in fume hood remove ethanol.Then support is freezed under -50 DEG C, vacuum condition
24 hours, obtain product β-TCP/10P-Unc porous supports.The size in hole is in 300-500 microns.Porosity is 90 ± 2%.Most
Big compressive strength is 0.02 ± 0.01MPa, and tear type variable is 120 ± 32%.
Embodiment 4
The preparation of β-TCP/15P-Unc porous supports
By obtained PGS performed polymers (PGS-1:1, prepared by embodiment 1) concentration that is made into absolute ethyl alcohol as solvent is
17.5mg/ml solution.β-TCP porous supports (weight 0.2g) is placed in 24 orifice plates, PGS solution 2ml are added, makes support complete
Full submergence, is then placed in orifice plate 3～5 hours in fume hood, and ethanol volatilization is most of.Then by support in -30 DEG C, vacuum
Under the conditions of freeze 24 hours, obtain product β-TCP/15P-Unc porous supports.The size in hole is in 300-500 microns.Porosity is
85 ± 2%.Greatest compressive strength is 0.03 ± 0.01MPa, and tear type variable is 180 ± 26%.
Embodiment 5
The preparation of β-TCP/25P-Unc porous supports
By obtained PGS performed polymers (PGS-1:1, prepared by embodiment 1) concentration that is made into absolute ethyl alcohol as solvent is
33.5mg/ml solution.β-TCP porous supports (weight 0.2g) is placed in 24 orifice plates, PGS solution 2ml are added, support is soaked
Not yet, then orifice plate is placed in 3～5 hours in fume hood, ethanol volatilization is most of.Then by support in -30 DEG C, vacuum condition
Freeze 24 hours down, obtain product β-TCP/25P-Unc porous supports.The size in hole is in 300-500 microns.Porosity be 75 ±
5%.Greatest compressive strength is 0.04 ± 0.01MPa, and tear type variable is 150 ± 22%.
Embodiment 6
The preparation of β-TCP/10P-C porous supports
By obtained PGS performed polymers (PGS-1:1, prepared by embodiment 1) concentration that is made into absolute ethyl alcohol as solvent is
10.0mg/ml solution.β-TCP porous supports (weight 0.2g) is placed in 24 orifice plates, PGS solution 2ml are added, support is soaked
Not yet, then orifice plate is placed in 3～5 hours in fume hood, ethanol volatilization is most of.Then support is placed on into vacuum drying chamber
In, 130 DEG C, vacuum, under conditions of 48 hours, obtain product β-TCP/10P-C porous supports.The size in hole is micro- in 300-500
Rice.Porosity is 90 ± 2%.Greatest compressive strength is 0.18 ± 0.02MPa, and tear type variable is 144 ± 13%.
Embodiment 7
The preparation of β-TCP/15P-C porous supports
By obtained PGS performed polymers (PGS-1:1, prepared by embodiment 1) concentration that is made into absolute ethyl alcohol as solvent is
17.5mg/ml solution.β-TCP porous supports (weight 0.2g) is placed in 24 orifice plates, PGS solution 2ml are added, support is soaked
Not yet, then orifice plate is placed in 3～5 hours in fume hood, ethanol volatilization is most of.Then support is placed on into vacuum drying chamber
In, 130 DEG C, vacuum, under conditions of 48 hours, obtain product β-TCP/15P-C porous supports.The size in hole is micro- in 300-500
Rice.Porosity is 88 ± 3%.Greatest compressive strength is 0.32 ± 0.03MPa, and tear type variable is 220 ± 12%.
Embodiment 8
The preparation of β-TCP/25P-C porous supports
By obtained PGS performed polymers (PGS-1:1, prepared by embodiment 1) concentration that is made into absolute ethyl alcohol as solvent is
33.5mg/ml solution.β-TCP porous supports (weight 0.2g) is placed in 24 orifice plates, PGS solution 2ml are added, support is soaked
Not yet, then orifice plate is placed in 3～5 hours in fume hood, ethanol volatilization is most of.Then support is placed on into vacuum drying chamber
In, 130 DEG C, vacuum, under conditions of 48 hours, obtain product β-TCP/25P-C porous supports.The size in hole is micro- in 300-500
Rice.Porosity is 75 ± 5%.Greatest compressive strength is 0.25 ± 0.02MPa, and tear type variable is 257 ± 30%.
Embodiment 9
The preparation of β-TCP/10P-CFV porous supports
By obtained PGS performed polymers (PGS-1:1, preparing by embodiment 1) concentration that is made into absolute ethyl alcohol as solvent is
10.0mg/ml solution.β-TCP porous supports (weight 0.2g) is placed in 24 orifice plates, PGS solution 2ml are added, support is soaked
Not yet, then orifice plate is placed in 3～5 hours in fume hood, ethanol volatilization is most of.Then support is placed on into vacuum drying chamber
In, 130 DEG C, vacuum, under conditions of 48 hours, then support is positioned over again in vacuum freeze drier, -50 DEG C, vacuum, 24
Under conditions of hour, product β-TCP/10P-CFV porous supports are obtained.The size in hole is in 300-500 microns.Porosity be 90 ±
2%.Greatest compressive strength is 0.42 ± 0.02MPa, and tear type variable is 185 ± 15%.
The preparation of the β-TCP/15P-CFV porous supports of embodiment 10
10.1 prepare
By obtained PGS performed polymers (PGS-1:1, preparing by embodiment 1) concentration that is made into absolute ethyl alcohol as solvent is
17.5mg/ml solution.β-TCP porous supports (weight 0.2g, pattern is as shown in Figure 3) is placed in 24 orifice plates, adds PGS molten
Liquid 2ml, makes support submergence, and then orifice plate is placed in 3～5 hours in fume hood, and ethanol volatilization is most of.Then support is put
Put in vacuum drying chamber, 130 DEG C, vacuum, under conditions of 48 hours, then support is positioned over again vacuum freeze drier
In, -50 DEG C, vacuum, under conditions of 24 hours, obtain product β-TCP/15P-CFV porous supports, can also be labeled as β-TCP/
15PGS-CFV/-50℃。
In porous support pattern such as Fig. 3 shown in d.
SEM is schemed as shown in C in Fig. 4 and D.
TGA and XRD are as shown in Figure 5.
As a result show that PGS is compound to β-TCP porous scaffold surfaces, content is 15%, maintain good hole connection
Property and uniform-dimension aperture, average pore size be 300-500 microns.D figures in Fig. 4 can see that PGS is more negative than more uniform
It is loaded in the surface of β-TCP, and has been bonded in the particle of β-TCP is stronger together.Porosity is 89 ± 3%.
Fig. 6 illustrates that the compound rest prepared to simple β-TCP porous supports and embodiment 10 carries out the result of manual compression
Figure, wherein being the compression result to simple β-TCP porous supports for A, as a result shows, has handled dynamic pressure contracting after-poppet substantially
Original pattern can not be kept, and becomes powder；B is the result figure that manual compression is carried out to compound rest, as a result table
Bright, handling dynamic pressure contracting after-poppet can substantially be completely recovered to original pattern.This also can be shown that porous compound support frame is compared
Single TCP porous support mechanical properties have obtained very big raising, improve the fragility of TCP porous supports.
Additionally, after testing greatest compressive strength is 1.73 ± 0.1MPa, tear type variable is 375 ± 25%.
10.2 permeability experiments
Permeability experiment, concrete steps are carried out to the support that embodiment 2 and 10 is obtained with methyl amine indigo plant：Each support drop
Plus the solution of 2ml, infiltration situation is observed after 5s, 30s, by support from middle incision after 60s.
As a result as shown in A in Fig. 7, wherein upper figure is the test chart of simple β-TCP porous supports, figure below is compound rest
Test chart.Show connective equally with very high hole using the compound after-poppets of PGS.
Embodiment 11
The preparation of β-TCP/25P-CFV porous supports
By obtained PGS performed polymers (PGS-1:1, preparing by embodiment 1) concentration that is made into absolute ethyl alcohol as solvent is
33.5mg/ml solution.β-TCP porous supports (weight 0.2g) is placed in 24 orifice plates, PGS solution 2ml are added, support is soaked
Not yet, then orifice plate is placed in 3～5 hours in fume hood, ethanol volatilization is most of.Then support is placed on into vacuum drying chamber
In, 130 DEG C, vacuum, under conditions of 48 hours, then support is positioned over again in vacuum freeze drier, -50 DEG C, vacuum, 24
Under conditions of hour, product β-TCP/25P-CFV porous supports are obtained.The size in hole is in 300-500 microns.Porosity is 75
± 5%.
The porosity of porous support materials is determined according to drainage, computing formula is as follows：
Porosity P=(W2-W3+WS)/(W1-W3)
Wherein WSFor sample quality, W1To weigh the quality of the specific gravity bottle full of absolute ethyl alcohol；W2It is that sample is put into into proportion
Gross mass in bottle；W3Be sample is taken out after, the quality of specific gravity bottle.
As a result as shown in B in Fig. 7, porosity 90-95% of simple β-TCP supports (being obtained by embodiment 2)；β-TCP/
The porosity 90 ± 2% of 10P-CFV supports (being obtained by embodiment 9)；β-TCP/15P-CFV supports (being obtained by embodiment 10)
Porosity 89 ± 3%；The porosity 75 ± 5% of β-TCP/25P-CFV supports (being obtained by embodiment 11).
After testing, greatest compressive strength is 0.94 ± 0.1MPa, and tear type variable is 640 ± 70%.
Embodiment 12
The preparation of-TCP/15P-CF/25 DEG C of porous support of β
By obtained PGS performed polymers (PGS-1:1, preparing by embodiment 1) concentration that is made into absolute ethyl alcohol as solvent is
17.5mg/ml solution.β-TCP porous supports (weight 0.2g) is placed in 24 orifice plates, PGS solution 2ml are added, support is soaked
Not yet, then orifice plate is placed in 3～5 hours in fume hood, ethanol volatilization is most of.Then support is placed on into vacuum drying chamber
In, 130 DEG C, vacuum, under conditions of 48 hours, then support is positioned over again in drying machine, 25 DEG C, under conditions of 24 hours,
Obtain-TCP/15P-CF/25 DEG C of porous support of product β.The size in hole is in 300-500 microns.Porosity is 90 ± 2%.It is maximum
Compressive strength is 0.32 ± 0.05MPa, and tear type variable is 220 ± 12%.
Embodiment 13
The preparation of-TCP/15P-CF/-20 DEG C of porous support of β
By obtained PGS performed polymers (PGS-1:1, preparing by embodiment 1) concentration that is made into absolute ethyl alcohol as solvent is
17.5mg/ml solution.β-TCP porous supports (weight 0.2g) is placed in 24 orifice plates, PGS solution 2ml are added, support is soaked
Not yet, then orifice plate is placed in 3～5 hours in fume hood, ethanol volatilization is most of.Then support is placed on into vacuum drying chamber
In, 130 DEG C, vacuum, under conditions of 48 hours, then support is positioned over again in freeze drier, -20 DEG C, the bar of 24 hours
Under part ,-TCP/15P-CF/-20 DEG C of porous support of product β is obtained.The size in hole is in 300-500 microns.Porosity be 88 ±
2%.Greatest compressive strength is 0.04 ± 0.05MPa, and tear type variable is 250 ± 15%.
Embodiment 14
The preparation of-TCP/15P-CF/-50 DEG C of porous support of β
By obtained PGS performed polymers (PGS-1:1, preparing by embodiment 1) concentration that is made into absolute ethyl alcohol as solvent is
17.5mg/ml solution.β-TCP porous supports (weight 0.2g) is placed in 24 orifice plates, PGS solution 2ml are added, support is soaked
Not yet, then orifice plate is placed in 3～5 hours in fume hood, ethanol volatilization is most of.Then support is placed on into vacuum drying chamber
In, 130 DEG C, vacuum, under conditions of 48 hours, then support is positioned over again in freeze drier, -50 DEG C, the bar of 24 hours
Under part ,-TCP/15P-CF/-50 DEG C of porous support of product β is obtained.The size in hole is in 300-500 microns.Porosity be 89 ±
2%.Greatest compressive strength is 0.78 ± 0.05MPa, and tear type variable is 280 ± 22%.
Embodiment 15
The preparation of-TCP/15P-CF/-80 DEG C of porous support of β
By obtained PGS performed polymers (PGS-1:1, preparing by embodiment 1) concentration that is made into absolute ethyl alcohol as solvent is
17.5mg/ml solution.Simple β-TCP porous supports (weight 0.2g) are placed in 24 orifice plates, PGS solution 2ml are added, make to prop up
Frame submergence, is then placed in orifice plate 3～5 hours in fume hood, and ethanol volatilization is most of.Then support is placed on into vacuum to do
In dry case, 130 DEG C, vacuum, under conditions of 48 hours, then support is positioned over again in -80 DEG C of refrigerator, -80 DEG C, 24 hours
Under conditions of, obtain-TCP/15P-CF/-80 DEG C of porous support of product β.The size in hole is in 300-500 microns.Porosity is 85
± 2%.Greatest compressive strength is 0.32 ± 0.03MPa, and tear type variable is 268 ± 20%.
Embodiment 16
The preparation of-TCP/15P-CF/-190 DEG C of porous support of β
By obtained PGS performed polymers (PGS-1:1, preparing by embodiment 1) concentration that is made into absolute ethyl alcohol as solvent is
17.5mg/ml solution.Simple β-TCP porous supports (weight 0.2g) are placed in 24 orifice plates, PGS solution 2ml are added, are made
Support submergence, is then placed in orifice plate 3～5 hours in fume hood, and ethanol volatilization is most of.Then support is placed on into vacuum
In drying box, 130 DEG C, vacuum, under conditions of 48 hours, then support is positioned over again in -190 DEG C of liquid nitrogen, -190 DEG C, 2
Under conditions of minute ,-TCP/15P-CF/-190 DEG C of porous support of product β is obtained.The size in hole is in 300-500 microns.Porosity
For 87 ± 3%.Greatest compressive strength is 0.20 ± 0.09MPa, and tear type variable is 230 ± 18%.
Embodiment 17
The preparation of-TCP/15PCL-CFV/-50 DEG C of porous support of β
The PCL of purchase is made into into concentration for 17.5mg/ml solution.Single pure β-TCP porous supports (weight 0.2g) are put
Put in 24 orifice plates, add PCL solution 2ml, make support submergence, then orifice plate is placed in 3～5 hours in fume hood, by ethanol
Volatilization is most of.Then support is placed in vacuum drying chamber, 130 DEG C, vacuum, under conditions of 48 hours, then by support
It is positioned over again in -50 DEG C of vacuum freeze dryer, -50 DEG C, vacuum, under conditions of 24 hours, obtain product β-TCP/
15PCL-CFV/-50 DEG C of porous support.The size in hole is in 300-500 microns.Porosity is 80 ± 5%.Greatest compressive strength is
0.43 ± 0.08MPa, tear type variable is 125 ± 16%.
Embodiment 18
The preparation of-TCP/15PLA-CFV/-50 DEG C of porous support of β
PLA is made into into concentration for 17.5mg/ml solution.Single pure β-TCP porous supports (weight 0.2g) are placed on into 24
In orifice plate, PLA solution 2ml are added, make support submergence, then orifice plate is placed in 3～5 hours in fume hood, ethanol volatilization is big
Part.Then support is placed in vacuum drying chamber, 130 DEG C, vacuum, under conditions of 48 hours, then again place support
In -50 DEG C of vacuum freeze dryer, -50 DEG C, vacuum, under conditions of 24 hours, obtain product β-TCP/15PLA-CFV/-
50 DEG C of porous supports.The size in hole is in 300-500 microns.Porosity is 82 ± 3%.Greatest compressive strength be 0.58 ±
0.1MPa, tear type variable is 187.5 ± 12%.
Embodiment 19
β-TCP/PGS compound support frame material mechanical properties
β-TCP/PGS compound support frame materials are prepared into the rectangle batten of 10mm × 10mm × 10mm, then in universal material
(AG-2000A, Shimadzu, Japan) carries out compression test on testing machine, and compression speed is 1mm/min.
As a result as shown in Fig. 8 and Biao 1.
The mechanical experimental results of table 1
As a result show, compared with simple β-TCP supports (preparing by embodiment 2), through heat cure crosslinking and -50 DEG C of vacuum
Two steps are obtained under freeze-drying PGS/ β-TCP supports (preparing by embodiment 9,10 and 11), it is crosslinked through heat cure and obtains
PGS/ β-TCP supports (by embodiment 4,5 and 6 prepare) and through vacuum freeze drying PGS/ β-TCP supports (press embodiment
3rd, 4 and 5 prepare) mechanical property be significantly increased.Especially two steps are obtained under heat cure crosslinking and -50 DEG C of vacuum freeze dryings
PGS/ β-TCP the supports (preparing by embodiment 9,10 and 11) for obtaining, with the PGS/ β-TCP supports obtained through heat cure crosslinking
(preparing by embodiment 4,5 and 6) and PGS/ β-TCP supports (preparing by embodiment 3, the 4 and 5) phase through vacuum freeze drying
Than mechanical property is also significantly improved.
Specifically, compared with β-TCP supports, the maximum compression of β-TCP/15P-CFV supports (being obtained by embodiment 10) is strong
Degree improves about 200 times of (β-TCP/15P-CFV, 1.730 ± 0.100MPa；β-TCP, 0.01 ± 0.002MPa), fracture deformation
Amount improves 3.7 times of (β-TCP/15P-CFV, 375 ± 25%, β-TCP:102 ± 1%).
Even if using identical preparation technology, the compound rest (embodiment prepared with different macromolecule PCL and PLA
17 and embodiment 18), compared with the compound rest prepared using PGS, greatest compressive strength is low 4 and 3 times.The knot of tear type variable
Fruit also indicates that the toughness of β-TCP/15P-CFV supports prepared by embodiment 10 is (real far above corresponding PCL and PLA compound rests
Apply example 17 and embodiment 18).That is the introducing of organic polymer PGS, and it is dry by heat cure crosslinking and vacuum refrigeration
The mechanical strength of β-TCP porous support materials can be extremely significantly increased after dry.
Embodiment 20
The Bioactivity of β-TCP/PGS compound support frame materials
20.1pH stability tests
β-TCP supports (prepared by embodiment 2) and β-TCP/PGS compound support frame materials (preparation of embodiment 9,10,11) are soaked
In Tris-HCl, test solution is in the different time sections pH value of 1,3,7,14,21 days and the weight of support for bubble.
As a result as shown in Figure 9 A, it is found that in the range of experimental period, β-TCP/15P-CFV (embodiment 10) immersions
Tris-HCl solution ph it is stable between 7.0～7.2, illustrate that it has good pH stability.And β-TCP (embodiments
2) constantly increase with time lengthening with the Tris-HCl solution ph of the immersion of β-TCP/10P-CFV (embodiment 9), solution is in
Meta-alkalescence.The Tris-HCl solution ph of β-TCP/25P-CFV (embodiment 11) immersions constantly reduces with time lengthening, and solution is most
Slant acidity afterwards.
B results show in Fig. 9, and PGS contents can also affect the degraded of material.The degraded of pure TCP supports is slower, and PGS
Being combined can to a certain extent accelerate the degraded of support.
20.2 external mineralization ability tests
β-TCP supports (prepared by embodiment 2) and β-TCP/PGS compound support frame materials (preparation of embodiment 9,10,11) are soaked
In human body simulation body fluid, (SBF accurately weighs reagent and in strict accordance with following order and consumption to bubble using electronic analytical balance：
7.996g NaCl, 0.353g NaHCO3,0.224g KCl,0.228g K2HPO43H2O,0.305g MgCl26H2O,0.045g
HCl,0.278g CaCl20.071g Na2SO4,6.057g CNH2(CH2OH)3) in.
As a result as shown in Figure 10, wherein A is single β-TCP supports (preparing by embodiment 2)；B is β-TCP/10P-CFV
(embodiment 10 is obtained)；C is β-TCP/15P-CFV (embodiment 10 is obtained)；D is β-TCP/15P-CFV (embodiment 11 is obtained).
By SEM can with phenetic analysis Ca/P timbering material surface deposition conditions.
By the mineralising of 3 days after, single β-TCP supports deposition occurs in that the surface that nano particle is distributed, but adds
PGS and content are that 25% compound rest β-TCP/25P-CFV are changed greatly, i.e., surface presents the similar-TCP/15P- containing β
The pattern of the nanofiber of CFV supports.When the increase of the content with PGS, the nanofiber of rack surface also becomes longer.
The result of EDS shows, under the conditions of same mineralising, all of sample surfaces all deposited identical Ca/P structures
Chemical composition.In compound rest, β-TCP/15P-CFV supports compare other supports and have shown best mineralising result.
PGS possesses more hydroxyl and carbonyl, can promote the Ca in simulated solution2+Deposit on support, which also promotes its mineralising.
Because the surface energy of β-TCP/PGS compound support frame materials occurs rapidly a series of physical-chemical reaction, cause it
Surface forms one layer of carbonate hydroxyapatite similar to skeleton inorganic phase (HAP), so as to, soft tissue such as glue hard with human body
Former albumen and cell further into key joint, therefore compared with simple β-TCP porous supports, β-TCP/PGS prepared by the present invention
Compound support frame material has more excellent external mineralization ability and biologically active.
Embodiment 21
The cell compatibility of β-TCP/PGS compound support frame materials
The present embodiment with mouse mesenchymal stem cells MSCs (rBMSCs) and endothelial cell (HUVEC) as model, using mtt assay
The cytoactive of timbering material prepared by detection embodiment 2 and 10,11.
Mouse mesenchymal stem cells MSCs preparation process：1st, rat 100g or so, takes off neck and puts to death, 75% alcohol bubble 10min.2、
Aseptic stripping femur, shin bone, then shell the muscle on bone to the greatest extent with gauze.3rd, metaphysis is cut off, is drawn with 5ml syringes and is contained 10%
Hyclone (not inactivating) L-DMEM culture mediums rinse ossis, blow and beat the single cell suspension of system.4th, be centrifuged 1000r/min, from
Heart 5min.5th, supernatant is abandoned, culture medium re-suspended cell blows and beats into cell suspension, is seeded in blake bottle and cultivates
Mtt assay：Cell (2 × 10 will be inoculated with4Individual/hole) timbering material be incubated in 24 orifice plates, per hole add 100 μ L
Tetramethyl azo azoles salt reagent, 37 DEG C are continued to be incubated after 4h, and supernatant is abandoned in suction, adds 1mL DMSO, gently shakes 20min,
Crystal is dissolved, the absorbance value of solution is determined after centrifugation at 490nm using continuous spectrum ELIASA.
Cytoactive and cell propagation such as Figure 11 that mtt assay is measured, it is seen that increase over time, cytoactive is good,
With good biocompatibility.
By laser co-focusing (confocal laser scanning microscopy) observation of cell in embodiment 10
Infiltration on the compound support frame material of preparation and sprawl：By 2*104The cell culture in individual/hole PBS three after 24h on material
Secondary, 2.5% glutaraldehyde is fixed after 15min and dyeed with the phalloidine (FITC-Phalloidin) of marked by fluorescein isothiocyanate
40 minutes, PBS 5 times, each 5min carried out three dimensional viewing after mounting fluid-tight piece under laser co-focusing.
As a result such as Figure 12, it is seen that porous support materials are conducive to the infiltration of cell and grow into, and show good cell
Adhesion and compatibility.
The all documents referred in the present invention are all incorporated as in this application reference, independent just as each document
It is incorporated as with reference to such.In addition, it is to be understood that after the above-mentioned instruction content for having read the present invention, those skilled in the art can
To make various changes or modifications to the present invention, these equivalent form of values equally fall within the model that the application appended claims are limited
Enclose.
Claims (37)
1. a kind of bata-tricalcium phosphate/poly- decanedioic acid glyceride compound rest, it is characterised in that the compound rest is by poly- decanedioic acid
Glyceride and bata-tricalcium phosphate porous support are constituted, and it is many that the compound rest is compounded in bata-tricalcium phosphate by poly- decanedioic acid glyceride
Constitute on the support of hole, the compound rest includes：The poly- decanedioic acid glyceride of 10～25wt% and 75-90wt% bata-tricalcium phosphates,
With the gross weight meter of the compound rest,
Also, the bata-tricalcium phosphate porous support porosity is 70%-95%, the average hole of the bata-tricalcium phosphate porous support
Footpath is 300-500 microns.
2. compound rest as claimed in claim 1, it is characterised in that the porosity of the compound rest is 70%-95%.
3. compound rest as claimed in claim 1, it is characterised in that the average pore size of the compound rest is that 300-500 is micro-
Rice.
4. compound rest as claimed in claim 1, it is characterised in that can bear most before the compound rest structure destruction
Big compressive strength is 0.015-2MPa.
5. compound rest as claimed in claim 1, it is characterised in that can occur most before the compound rest structure destruction
Large deformation amount is 120%-750%.
6. compound rest as claimed in claim 1, it is characterised in that in the compound rest, the bata-tricalcium phosphate and institute
The mass ratio for stating poly- decanedioic acid glyceride is 1：0.1-0.35.
7. compound rest as claimed in claim 1, it is characterised in that porosity is 85-95%.
8. compound rest as claimed in claim 1, it is characterised in that porosity is 90-95%.
9. compound rest as claimed in claim 1, it is characterised in that the bata-tricalcium phosphate and the poly- decanedioic acid glyceride
Mass ratio be 1：0.18.
10. compound rest as claimed in claim 1, it is characterised in that the bata-tricalcium phosphate porous support by nano beta-
Tricalcium phosphate is made, and the average grain diameter of the nanoscale bata-tricalcium phosphate is 300-500 nanometers.
The preparation method of 11. compound rests as claimed in claim 1, it is characterised in that the preparation method includes following step
Suddenly：
A bata-tricalcium phosphate porous support impregnated in and obtain in poly- decanedioic acid glyceride prepolymer solution bata-tricalcium phosphate/poly- by ()
Decanedioic acid glyceride compound rest；
B step (a) acquisition bata-tricalcium phosphate/poly- decanedioic acid glyceride compound rest heat cross-linking is obtained being crosslinked support by ()；
C crosslinking support that () obtains step (b) is dried to obtain the compound rest.
12. preparation method as claimed in claim 11, it is characterised in that the poly- decanedioic acid glyceride prepolymer solution it is dense
Spend for 10-35mg/ml, the bata-tricalcium phosphate is 1 with the mass ratio of the poly- decanedioic acid glyceride performed polymer：0.1-0.35.
13. preparation methods as claimed in claim 11, it is characterised in that the bata-tricalcium phosphate and the poly- decanedioic acid glycerine
The mass ratio of ester performed polymer is 1：0.18.
14. preparation methods as claimed in claim 11, it is characterised in that used by the poly- decanedioic acid glyceride prepolymer solution
Solvent is alcohols solvent, dimethyl sulfoxide (DMSO), chloroform, dichloromethane.
15. preparation methods as claimed in claim 11, it is characterised in that the bata-tricalcium phosphate porous support by nano beta-
Tricalcium phosphate is made, and the average grain diameter of the nanoscale bata-tricalcium phosphate is 300-500 nanometers.
16. preparation methods as claimed in claim 11, it is characterised in that β-tricresyl phosphate is prepared using polyurethane foam infusion process
Calcium porous support.
17. preparation methods as claimed in claim 11, it is characterised in that bata-tricalcium phosphate solution and solvent are mixed and made into into slurry
Material, makes in the slurry slurry uniformly be poured into foam polyurethane foam dipping, treats that solvent is evaporated completely from the foam for having irrigated
Foam is sintered after complete, removed polyurethane foam and is obtained bata-tricalcium phosphate porous support.
18. preparation methods as claimed in claim 11, it is characterised in that the preparation bag of the poly- decanedioic acid glyceride performed polymer
Include following steps：
It is 1 by mol ratio under the atmosphere of (i) argon gas:1 decanedioic acid and glycerine react 18-36 hours at 120-140 DEG C；
(ii) 18-36 hours under the product of step (i) being placed in into 120-140 DEG C, vacuum condition, obtain thick PGS performed polymers；
(iii) the thick PGS performed polymers that dialysis purification step (ii) is obtained obtain the described poly- decanedioic acid glyceride performed polymer for purifying.
19. preparation methods as claimed in claim 11, it is characterised in that the molecular weight of the poly- decanedioic acid glyceride performed polymer
For 12000 dalton.
20. preparation methods as claimed in claim 11, it is characterised in that the disperse system of the poly- decanedioic acid glyceride performed polymer
Number is 1.19.
21. preparation methods as claimed in claim 11, it is characterised in that the drying is referred to：
(1) vacuum freeze drying；
(2) it is vacuum dried；
(3) vacuum freeze drying after being vacuum dried；
(4) freeze after being vacuum dried.
22. preparation methods as claimed in claim 11, it is characterised in that also included solvent flashing before step (b) is dried
The step of.
23. preparation methods as claimed in claim 21, it is characterised in that the condition of (1) vacuum freeze drying is as follows：-
40 DEG C～-60 DEG C vacuum freeze drying 20-30 hours.
24. preparation methods as claimed in claim 21, it is characterised in that the condition of (1) vacuum freeze drying is as follows：-
50 DEG C of vacuum freeze dryings 24 hours.
25. preparation methods as claimed in claim 21, it is characterised in that (2) vacuum drying condition is as follows：120-
140 DEG C of vacuum drying 40-55 hours；Or (2) vacuum drying condition is as follows：120-140 DEG C of vacuum drying 40-55 is little
Shi Hou, 20-30 DEG C of vacuum drying 20-30 hour.
26. preparation methods as claimed in claim 21, it is characterised in that (2) vacuum drying condition is as follows：130℃
Vacuum drying 48 hours；Or (2) vacuum drying condition is as follows：After 130 DEG C are vacuum dried 48 hours, 25 DEG C of vacuum are done
Dry 24 hours.
27. preparation methods as claimed in claim 21, it is characterised in that vacuum freeze drying after described (3) vacuum drying
Condition is as follows：After 120-140 DEG C of vacuum drying 40-55 hour, -10 DEG C to -80 DEG C vacuum freeze drying 20-30 hours.
28. preparation methods as claimed in claim 21, it is characterised in that vacuum freeze drying after described (3) vacuum drying
Condition is as follows：After 130 DEG C of vacuum drying 48 hours, -20 DEG C to -50 DEG C vacuum freeze dryings 24 hours.
29. preparation methods as claimed in claim 21, it is characterised in that the condition freezed after described (4) vacuum drying is as follows：
- 80 DEG C to -200 DEG C are placed in after 120-140 DEG C of vacuum drying 40-55 hour to freeze -2 minutes 24 hours.
30. preparation method as claimed in claim 21, it is characterised in that the condition freezed after described (4) vacuum drying is as follows：
130 DEG C vacuum drying 48 hours after be placed in -80 DEG C to -200 DEG C freezing -2 minutes 24 hours.
31. a kind of pharmaceutical compositions, it is characterised in that described pharmaceutical composition is included：
Compound rest described in claim 1 or 2；With
For promoting the medicine and/or growth factor of Bone Defect Repari and/or growth.
32. pharmaceutical compositions as claimed in claim 31, it is characterised in that the medicine selected from dexamethasone, gentamicin,
Methotrexate (MTX), aceclofenac, 1,25- dihydroxyvitamin Ds, Lovastatin, simvastatin.
33. pharmaceutical compositions as claimed in claim 31, it is characterised in that the growth factor is selected from：There is egg in Bones morphology
White BMP, VEGF, Basic Fibroblast Growth Factor, TGF, hypoxia inducible transcription factor, BMP turn
Change growth factor family (TGFs), fibroblast growth factor (FGF), platelet derived growth factor (PDGF), insulin
Like growth factor (IGF).
34. a kind of tissue engineering bone renovation materials, it is characterised in that the tissue engineering bone renovation material is included：
Compound rest described in claim 1 or 2；With
For promoting the cell of Bone Defect Repari and/or growth.
35. repair materials as claimed in claim 34, it is characterised in that the cell is selected from：Mesenchymal stem cells MSCs and
Endothelial cell.
36. repair materials as claimed in claim 34, it is characterised in that the tissue engineering bone renovation material also includes promoting
Bone Defect Repari and/or the medicine and/or growth factor of growth.
The purposes of the pharmaceutical composition described in 37. compound rests as claimed in claim 1 or claim 31, its feature exists
In for preparing osseous tissue renovating material, as tissue engineering bracket material or as drug carrier material.
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| CN105999417B (en) * | 2016-06-03 | 2019-01-18 | 华东理工大学 | Human bone morphogenesis protein-2 composite material and preparation method and application |
| CN106139256A (en) * | 2016-07-28 | 2016-11-23 | 复旦大学附属中山医院 | Polylactic acid/nano β tricalcium phosphate complex stephanoporate bracket and preparation method thereof |
| WO2018209579A1 (en) * | 2017-05-17 | 2018-11-22 | 高雄医学大学 | Composite scaffold containing drug |
| CN111905156A (en) * | 2019-05-10 | 2020-11-10 | 华东理工大学 | High-strength absorbable active composite material and preparation method thereof |
| CN111956864A (en) * | 2020-08-18 | 2020-11-20 | 华东理工大学 | 3D printing composite support and preparation method and application thereof |
| CN117731830A (en) * | 2022-09-14 | 2024-03-22 | 华东理工大学 | Piezoelectric porous bracket with efficient bone promoting effect and preparation method thereof |
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| AU2007207495A1 (en) * | 2006-01-19 | 2007-07-26 | Warsaw Orthopedic, Inc. | Porous osteoimplant |
| CN101721740A (en) * | 2008-10-16 | 2010-06-09 | 上海国睿生命科技有限公司 | Bone tissue engineering bracket material and preparation method and application thereof |
| FR2942723B1 (en) * | 2009-03-05 | 2011-06-10 | Teknimes | CEMENT FOR BONE FILLING |
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